Lacosamide (SPM 927, also referred to as harkoseride or ADD 234037), is chemically (R)-2-acetamido-N-benzyl-3-methoxypropionamide of Formula Ia. It shows effects in the treatment of pain, epilepsy, fibromyalgia syndrome, osteoarthritis and migraine. It is also known to be useful for the treatment of CNS disorders in humans.

Lacosamide and its methods of preparation are disclosed in U.S. Reissue Pat. No. RE 38,551 (hereinafter referred to as the '551 patent). This reference provides three general methods for the preparation of lacosamide. The first two methods do not involve the protection of active groups in intermediate compounds (such as amino, hydroxy and carboxylic acid groups). The other method disclosed in the '551 patent involves protection of an amino group present in D-serine with carbobenzoxy chloride (Cbz-Cl), subsequent O-methylation at the hydroxy group followed by benzylamination at carboxylic (—COOH) group and finally removal of the ‘Cbz’ group followed by acetylation produces lacosamide.
An alternative method for the preparation of lacosamide is disclosed in PCT publication WO 2006/037574 (hereinafter referred to as '574 application) that involves O-methylation of N-Boc-protected-D-serine (“Boc” refers to t-butoxycarbonyl) directly in one step by avoiding simultaneous formation of the methyl ester moiety.
In view of the preparation methods available for lacosamide, there is a need for simple and cost effective processes for the preparation of lacosamide that eliminates racemization of intermediate compounds and final product and provides improved efficiency per reaction volume in terms of yield, purity and chiral purity.